(1) In order to study whether calretinin expression is coupled with neuronal activity, the effects of presynaptic denervation on calretinin protein and mRNA were examined in the auditory system. Unilateral ablations of the guinea pig cochlea produced an increase in calretinin mRNA in the ipsilateral anterior ventral cochlear nucleus one day post lesion. Immunohistochemical calretinin label was also increased at I and 7 days post surgery. Both calretinin protein and mRNA returned to normal by 56 days post lesion in the anterior ventral cochlear nucleus. In contrast, no effects on calretinin protein or mRNA were evident in the posterior ventral cochlear nucleus 1 day Post lesion. However, calretinin mRNA was significantly decreased by 56 days post lesion with a trend in the same direction at 7 days. There was a paradoxical increase in calretinin immunoreactivity in cells of the posterior ventral cochlear nucleus at both 7 and 56 days. These results suggest that calretinin expression is regulated by neuronal activity and that this regulation is most likely dependent on multiple factors including cell type and duration of recovery; (2) Calretinin mRNA was identified in peripheral receptor cells of the guinea pig and rat Organ of Corti; (3) Studies of the auditory brainstem of the developing chick embryo revealed a pattern of increased calretinin mRNA and immunohistochemical label from E9 to P10. The timing of calretinin expression coincided with the onset of neuronal activity for only some nuclei which receive direct input from the auditory nerve; (4) Changes were observed in calretinin mRNA in the substantia nigra compacta and in calbindin D-28k mRNA in the caudate by in situ hybridization in the genetically epilepsy prone rat.